Screening for Opioid and Stimulant Exposure In Utero Through Targeted and Untargeted Metabolomics Analysis of Umbilical Cords.

BACKGROUND: Neonatal abstinence syndrome is an array of signs and symptoms experienced by a newborn due to abrupt discontinuation of intrauterine exposure to certain drugs, primarily opioids. In the United States, the incidence of neonatal abstinence syndrome has tripled over the past decade. The current standard of care for drug testing includes the analysis of infant urine and meconium. Sample collection is associated with several limitations, including diaper media interferences, limited sample amount, sample heterogeneity, and the need for professional staff for collection. Umbilical cord tissue has emerged as a convenient sample matrix for testing owing to its universal availability. The purpose of this study was to examine umbilical cords using an untargeted metabolomics approach to determine the detected drugs and validate an analytical method to confirm and quantify the identified drugs. METHODS: A metabolomics analysis was performed with 21 umbilical cords to screen for drugs and drug metabolites by liquid chromatography-mass spectrometry. Drugs were identified using the National Institute of Standards and Technology database, and an analytical method was developed and validated using secondary liquid chromatography-mass spectrometry instrument for positive confirmation and quantitative analysis. RESULTS: Twenty-one random umbilical cords from women were tested: 4 were positive for cocaine and the primary and secondary metabolites; one was positive for methadone, the primary metabolite; 3 were positive for cotinine, the metabolite of nicotine; and 5 were positive for acetyl norfentanyl. CONCLUSIONS: Our research is a prospective method development study using untargeted and targeted approaches to characterize steady-state drug metabolite levels in the umbilical cord matrix at the time of delivery. By characterizing drug type and concentration, this methodology can be used to develop a reliable complementary testing method for meconium toxicology screens.

Influence of aerobic exercise on maternal lipid levels and offspring morphometrics.

BACKGROUND: Maternal BMI, lipid levels (cholesterol, triglyceride, LDL, HDL), and exercise amount are interrelated and each influence offspring body size. This study proposed to determine the influence of exercise on maternal lipid levels and infant body size. METHODS: We had 36 participants complete these measures. Participants in the aerobic exercise intervention (n = 14) completed three 50-min sessions weekly from 16 weeks gestation to delivery and were compared with a non-exercise control group (n = 22). Maternal lipid profiles were assessed at 16 and at 36 weeks gestation. Fetal body size was measured at 36 weeks gestational age using ultrasound assessment. Neonatal body size measures were acquired from birth records. Statistical analysis included two-sample t-tests, correlations, and regression models. RESULTS: Participants were similar in age, pre-pregnancy BMI, gravida, parity, education, and gestational weight gain (GWG). There were no differences in gestational age, Apgar scores at 1 and 5 min for infants of exercisers relative to controls. Exercisers had higher pre-training triglycerides (p = 0.004) and pregnancy change in triglycerides (p = 0.049) compared to controls. Head circumference was significantly larger in exercise exposed infants relative to infants of controls. Pregnancy METs had a positive relationship with birth length (r = .445, p = .006) and birth weight (r = .391, p = .02). GWG had a moderate, positive relationship with fetal abdominal circumference (r = .570, p = .004). Regression analysis indicated 5 predictors explained 61.7% of the variance in birth weight (Adj.R2 = 0.469, F(5,13) = 5,13, p = 0.02); it was found that pregnancy METs (ß = .724, p = .007), 36 week cholesterol (ß = 1.066, p = .02), and 36 week LDL (ß = -1.267, p = .006) significantly predict birth weight. Regression analysis indicated 4 predictors explained 43.8% of the variance in birth length (Adj.R2 = 0.306, F(4,17) = 3.32, p = 0.04); it was found that pregnancy METs (ß = .530, p = .03), and 36 week LDL (ß = -.891, p = .049) significantly predict birth length. CONCLUSION: The primary association and predictors of infant body size was related to pregnancy exercise and late pregnancy cholesterol and LDL levels. Considering these relationships, it is essential that women maintain aerobic exercise during pregnancy, but should also be cognizant of lipid levels during their pregnancy. Therefore intervention during pregnancy focused on infant body size should involve exercise and and quality nutritional intake foods during pregnancy.

Validity of a customized submaximal treadmill protocol for determining VO2max.

INTRODUCTION: A customized submaximal exercise test for cycle ergometry was reported as a superior estimate of maximum oxygen uptake (VO2max) in comparison to the traditional YMCA ergometry test. PURPOSE: Following similar methodology, we sought to validate a customized submaximal treadmill test (CustomTM) compared with the widely used Bruce submaximal protocol. METHODS: Participants (29 women and 21 men; age = 31.37 ± 11.44 year, BMI = 24.02 ± 3.03) performed a graded exercise test (GXT) with a subsequent exhaustive, square-wave bout for the verification of "true" VO2max. In counterbalanced order, subjects then completed submaximal protocols. The CustomTM protocol consisted of two 3-min stages estimated at 35 and 70% of VO2max, where VO2max was estimated with a linear regression equation utilizing sex, BMI, age, and self-reported physical activity. RESULTS: VO2 values from the GXT and verification bout were 47.2 ± 7.7 and 47.0 ± 7.7 ml kg-1 min-1, respectively (ICC = 0.99, CV = 2.0%, TE = 0.83 ml kg-1 min-1), with the highest value used as "true" VO2max (47.7 ± 7.7 ml kg-1 min-1). Neither the Bruce (45.95 ± 6.97 ml kg-1 min-1) nor the CustomTM (47.3 ± 9.4 ml kg-1 min-1) protocol differed from "true" VO2max. The CustomTM had a "very large" measurement agreement with "true" VO2max (ICC = 0.78, CV of 9.1%, TE = 4.07 ml kg-1 min-1). Bruce had a "large" measurement agreement with "true" VO2max (ICC = 0.62, CV of 10.0%, TE = 4.51 ml kg-1 min-1). CONCLUSION: The CustomTM was superior to the Bruce protocol, because it included a stage below and above gas exchange threshold, yielded a better measurement agreement for "true" VO2max, and was more time efficient.

Normative Data for Critical Speed and D' for High-Level Male Rugby Players.

Kramer, M, Clark, IE, Jamnick, N, Strom, C, and Pettitt, RW. Normative data for critical speed and D' for high-level male rugby players. J Strength Cond Res 32(3): 783-789, 2018-The critical speed (CS) concept helps characterize the aerobic and anaerobic fitness of an athlete. Rugby players should, hypothetically, have modest CS values but extremely high curvature constant (D') values, yet, normative data are currently unavailable. To develop normative data of CS and D' for high-level male rugby players, a total of 30 male rugby players were recruited from the Eastern Cape of South Africa. All subjects performed the running 3-minute all-out exercise test (3 MT) using global positioning system (GPS) technology to determine CS and D'. The GPS data were used to determine the total distance and velocities performed, and to examine for pacing effects. Summary statistics of mean ± SD are provided. High total running speeds for the initial 150 seconds (S150s = 5.79 ± 0.59 m·s), and total distance (3 MT distance = 871.5 ± 71.9 m) were observed. A total of 13 of 30 subjects surpassed the 300 m D' value (mean D' = 288.2 ± 49.1 m). The CS of the total group was 3.87 ± 0.55 m·s. All 3 MT-derived data were categorized using standard nine (stanine) tables that allowed for the generation of normative data with which future performances, performances across similar sporting domains, and more accurate contrasts across the literature can be compared. Skewing of CS and D' was observed between forwards and backs, therefore, between-group differences in neither CS nor D' were observed (p > 0.05). Comparisons with previous literature indicate that male rugby players have higher CS values than female rugby players. When compared with Olympic distance runners, male rugby players have markedly higher D' values and markedly lower CS values. The 3 MT provides a useful procedure for assessing and prescribing high-intensity interval training for rugby athletes.

Exercise FITT-V during pregnancy: Association with birth outcomes.

BACKGROUND: Prenatal exercise improves birth outcomes, but research into exercise dose-response effects is limited. METHODS: This study is a retrospective, secondary analysis of pooled data from three blinded, prospective, randomized controlled trials. Prenatal exercise frequency, intensity, type, time, and volume (FITT-V) were assessed in supervised sessions throughout pregnancy. Gestational age (GA), neonatal resting heart rate (rHR), morphometrics (body circumferences, weight-to-length and ponderal index) Apgar and reflex scores, and placental measures were obtained at birth. Stepwise regressions and Pearson correlations determined associations between FITT-V and birth outcomes. RESULTS: Prenatal exercise frequency reduces ponderal index (R2 = 0.15, F = 2.76, p = .05) and increased total number of reflexes present at birth (R2 = 0.24, F = 7.89, p < .001), while exercise intensity was related to greater gestational age and birth length (R2 = 0.08, F = 3.14; R2 = 0.12, F = 3.86, respectively; both p = .04); exercise weekly volume was associated with shorter hospital stay (R2 = 0.24, F = 4.73, p = .01). Furthermore, exercise type was associated with placenta size (R2 = 0.47, F = 3.51, p = .01). CONCLUSIONS: Prenatal exercise is positively related to birth and placental outcomes in a dose-dependent manner.

Influence of Supervised Maternal Aerobic Exercise during Pregnancy on 1-Month-Old Neonatal Cardiac Function and Outflow: A Pilot Study.

PURPOSE: The objective of this study is to assess the effects of supervised, recommended levels of prenatal aerobic exercise on 1-month-old infant cardiac function. METHODS: Eligible pregnant women were randomly assigned to either an aerobic exercise group that participated in 150 min of supervised, moderate-intensity (40% to 59% V̇O 2peak , 12 to 14 on Borg rating of perceived exertion) aerobic exercise per week for 24 wk or more or a nonexercising group that consisted of 150 min·wk -1 of relaxation techniques. One-month-old infant echocardiogram was performed to assess infant cardiac function , including heart rate (HR), left-ventricular stroke volume, cardiac output, cardiac index, ejection fraction, fractional shortening, and velocity time integral at the aortic valve. Pearson correlation analyses and linear regression models were performed. RESULTS: Prenatal aerobic exercise was negatively correlated with infant resting HR ( r = -0.311, P = 0.02). Similarly, when controlling for infant sex and activity state, exercise level/volume ( ß = -0.316; 95% CI, -0.029 to -0.002; P = 0.02) predicted resting infant HR ( R2 = 0.18, P = 0.02). In infants of overweight/obese women, infants of aerobic exercisers had increased fractional shortening ( P = 0.03). In addition, infant ventricular ejection fraction was correlated with maternal exercise attendance ( r = 0.418, P = 0.03) as well as a trend for exercise level ( r = 0.351, P = 0.08). Similarly, the only significant regression model for infants of overweight/obese women controls infant activity state ( ß = -0.444; 95% CI, -0.05 to -0.01; P = 0.006) and maternal exercise level ( ß = 0.492; 95% CI, 5.46-28.74; P = 0.01) predicting infant resting HR ( F = 5.79, R2 = 0.40, P = 0.003). CONCLUSIONS: The findings of this study demonstrate that women participating in exercise in the second and third trimesters of their pregnancy may have infants with increased cardiac function at 1 month of age. Importantly, the cardiac function effects were further augmented for infants born to overweight/obese women.

Self-Reported Intake and Circulating EPA and DHA Concentrations in US Pregnant Women.

In the United States, pregnant women have low concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential for fetal development. Although maternal blood provides accurate polyunsaturated fatty acid (PUFA) concentrations, venipuncture is expensive and not always accessible. PUFA-containing foods consumption, both omega-3 ad omega-6 is supposed to reflect in the status (plasma, RBC, adipose tissue) of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). De novo synthesis of DHA and EPA during pregnancy is supposed to be higher compared to pre and/or post-pregnancy periods. Thus, this study aimed to determine the association between maternal self-reported dietary intake of foods high in DHA and EPA, along with vegetable oils as a source of omega-6 fatty acids, with maternal blood DHA and EPA concentrations. Pregnant women (13-16 weeks gestation) were recruited and asked to complete a food-frequency questionnaire (FFQ) and blood draw at enrollment and 36 weeks. Circulating concentrations of DHA and EPA were quantified and change scores were calculated. Correlations were done to determine associations between FFQ results and EPA/DHA maternal blood concentrations. Regression analyses were run to examine significant predictors of the main outcomes. Overall, PUFA-food consumption and RBC's DHA levels decreased from early to late pregnancy; self-reported PUFA-rich food consumption positively correlated with DHA and EPA levels. DHA concentration was predicted by self-reported PUFA-rich oils (sunflower/soy/corn/olive) consumption, but EPA concentration was predicted by maternal BMI. These findings suggest that EPA and DHA consumption decreased across pregnancy and the FFQ can be utilized as an effective method for estimating PUFA blood concentration during pregnancy.

Influence of exercise type on maternal blood pressure adaptation throughout pregnancy.

BACKGROUND: It has been reported that 10% of all pregnancies are complicated by a hypertensive disorder of pregnancy. Previous research has shown that moderate-vigorous intensity exercise has a positive effect on maternal resting blood pressure. A research gap, however, exists related to how different types of exercise (resistance, aerobic, combined resistance and aerobic) affect maternal blood pressure. Most of the previous studies solely focused on aerobic exercise. OBJECTIVE: The aim of this study was to examine the effects of exercise types on maternal blood pressure throughout pregnancy. STUDY DESIGN: This study employed a secondary analysis using data from a randomized controlled prenatal exercise intervention trial. This study utilized 3 exercise intervention groups (aerobic, resistance, combination) and compared the results with those of a nonexercize control group. Participants completed 3 50-minute sessions weekly from 16 weeks of gestation until delivery. Maternal vital signs and physical measurements such as systolic blood pressure, diastolic blood pressure, and heart rate were measured every 4 weeks throughout the intervention period. Between-group mean differences in maternal measurements were assessed using Pearson's chi-square tests for continuous (age, prepregnancy body mass index, heart rate, systolic blood pressure, diastolic blood pressure, pulse pressure) variables. For gravida, exact Wilcox 2-sample tests were performed to determine between-group differences in mean values. Hierarchical linear growth curves were used to estimate maternal trajectories of systolic blood pressure and diastolic blood pressure from 16 weeks to 36 weeks' gestation in each of the 4 groups (aerobic, combination, control, and resistance). RESULTS: There were no differences among the groups in maternal age or prepregnancy body mass index. Controlling for maternal body mass index, the lowest significant systolic blood pressure curve was noted throughout the pregnancy for women who participated in resistance exercise, followed by women in the aerobic exercise group all relative to the no exercise control group. At 36 weeks' gestation, the systolic blood pressure was lower in the resistance group by 12.17 mm Hg (P<.001) and in the aerobic group by 7.90 mm Hg (P<.001) relative to controls. No significant change in systolic blood pressure was noted in the combination group in comparison with controls at 36 weeks' gestation. Similarly, we demonstrated a significantly lower linear growth curve in diastolic blood pressure that was maintained throughout pregnancy in any exercise type relative to controls. After controlling for maternal body mass index, all 3 exercise types (combination, resistance, and aerobic) significantly predicted a similar decrease in diastolic blood pressure that was maintained throughout pregnancy. At 36 weeks' gestation, the diastolic blood pressure was lower in the aerobic group by 7.30 mm Hg (P<.01), in the combination group by 6.43 mm Hg (P<.05), and in the resistance group relative to controls. CONCLUSION: Overall, all exercise types were beneficial in lowering maternal resting blood pressure throughout pregnancy. Resistance training was noted to be the most beneficial in improving systolic blood pressure, followed by aerobic exercise. All 3 exercise groups were noted to improve diastolic blood pressure equally. Further research needs to be done to determine if either resistance or aerobic exercise throughout pregnancy decreases the risk for hypertensive disorders of pregnancy and the associated morbidity and mortality.

Maternal Aerobic Exercise, but Not Blood Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations, during Pregnancy Influence Infant Body Composition.

Although discrete maternal exercise and polyunsaturated fatty acid (PUFA) supplementation individually are beneficial for infant body composition, the effects of exercise and PUFA during pregnancy on infant body composition have not been studied. This study evaluated the body composition of infants born to women participating in a randomized control exercise intervention study. Participants were randomized to aerobic exercise (n = 25) or control (stretching and breathing) groups (n = 10). From 16 weeks of gestation until delivery, the groups met 3×/week. At 16 and 36 weeks of gestation, maternal blood was collected and analyzed for Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA). At 1 month postnatal, infant body composition was assessed via skinfolds (SFs) and circumferences. Data from 35 pregnant women and infants were analyzed via t-tests, correlations, and regression. In a per protocol analysis, infants born to aerobic exercisers exhibited lower SF thicknesses of triceps (p = 0.008), subscapular (p = 0.04), SF sum (p = 0.01), and body fat (BF) percentage (%) (p = 0.006) compared with controls. After controlling for 36-week DHA and EPA levels, exercise dose was determined to be a negative predictor for infant skinfolds of triceps (p = 0.001, r2 = 0.27), subscapular (p = 0.008, r2 = 0.19), SF sum (p = 0.001, r2 = 0.28), mid-upper arm circumference (p = 0.049, r2 = 0.11), and BF% (p = 0.001, r2 = 0.32). There were no significant findings for PUFAs and infant measures: during pregnancy, exercise dose, but not blood DHA or EPA levels, reduces infant adiposity.

The Influence of Maternal Aerobic Exercise, Blood DHA and EPA Concentrations on Maternal Lipid Profiles.

Exercise and polyunsaturated fatty acid (PUFA) supplementation independently improve lipid profiles. The influence of both exercise and PUFAs on lipids during pregnancy remains unknown. This study evaluated exercise, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations on lipids during pregnancy. Participants were randomized to aerobic exercise or control groups. From 16 weeks gestation until delivery, groups met 3x/week; exercisers performed moderate-intensity aerobic activity, controls performed low-intensity stretching and breathing. At 16 and 36 weeks' gestation, maternal blood was analyzed for lipids (total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG)), DHA and EPA. In intent-to-treat analysis, the aerobic group (n = 20), relative to controls (n = 10), exhibited a higher HDL change across gestation (p = 0.03). In a per protocol analysis, the aerobic group, relative to controls, exhibited 21.2% lower TG at 36 weeks (p = 0.04). After controlling for 36-week DHA and EPA, exercise dose predicts 36 weeks' TG (F (1,36) = 6.977, p = 0.012, r2 = 0.16). Aerobic exercise normalizes late pregnancy TG. During pregnancy, exercise dose controls the rise in TG, therefore maintaining normal levels. DHA and EPA do not have measurable effects on lipids. Regardless of PUFA levels, exercise at recommended levels maintains appropriate TG levels in pregnant women. Normal TG levels are critical for pregnancy outcomes, and further studies are warranted to investigate this association in broader populations.

Leisure-Time Physical Activity before and during Pregnancy Is Associated with Improved Insulin Resistance in Late Pregnancy.

A total of 83 third trimester pregnant women were recruited to examine the role of pre-pregnancy versus late-pregnancy physical activity on maternal insulin resistance. Principal component analysis plots demonstrated a distinction between the high and low Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) groups. The variation was driven primarily by exercise prior to and during pregnancy. Specifically, higher levels of physical activity prior to pregnancy was associated with a lower HOMA-IR and is not modified by other variables. Women who were active prior to pregnancy were more active during pregnancy. These results suggest that being active before pregnancy may be a good strategy for mitigating the risk of insulin resistance during late pregnancy.

The effects of aerobic exercise on markers of maternal metabolism during pregnancy.

BACKGROUND: Optimal maternal metabolism during pregnancy is essential for healthy fetal growth and development. Chronic exercise is shown to positively affect metabolism, predominantly demonstrated in nonpregnant populations. OBJECTIVE: To determine the effects of aerobic exercise on maternal metabolic biomarkers during pregnancy, with expected lower levels of glucose, insulin, and lipids among exercise-trained pregnant women. METHODS: Secondary data analyses were performed using data from two, longitudinal prenatal exercise intervention studies (ENHANCED by MOM and GESTAFIT). Exercisers completed 150 min of weekly moderate-intensity exercise during pregnancy (24+ weeks) while nonexercisers attended stretching sessions. Pregnant women were 31-33 years of age, predominantly non-Hispanic white, and "normal weight" body mass index. At 16 and 36 weeks of gestation, fasting blood samples were collected via fingerstick and venipuncture. Maternal glucose, insulin, insulin resistance (HOMA-IR), total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides (TG) were analyzed. ANCOVA analyses were performed to evaluate the effects of aerobic exercise on markers of maternal metabolism in late pregnancy, controlling for baseline levels. RESULTS: Our sample included 12 aerobic exercisers and 54 nonexercising control groups. Significant between-groups differences at 16 weeks of gestation were found for TG (92.3 vs. 121.2 mg/dl, p = .04), TC (186.8 vs. 219.6 mg/dl, p = .002), and LDL (104.1 vs. 128.8 mg/dl, p = .002). Aerobic-trained pregnant women exhibited lower insulin levels in late pregnancy (ß = -2.6 µIU/ml, 95% CI:-4.2, -0.95, p = .002) and a reduced increase in insulin levels from 16 to 36 week of gestation (ß = -2.3 µIU/ml, 95% CI: -4.4, -0.2, p = .034) compared with nonexercising pregnant women. No statistically significant effects were observed for maternal HOMA-IR, TC, LDL, HDL, TC:HDL, and TG in late pregnancy. CONCLUSIONS: The observations of this study demonstrate that prenatal exercise may positively affect maternal insulin, with aerobic-trained pregnant women exhibiting lower insulin levels in late pregnancy. Additionally, we found no appreciable effects of prenatal exercise on maternal lipids in late pregnancy.